Microfluidic devices and “microscopic” fluid handling systems are becoming essential in many important fields. The advantages of fast response times, easy integration, and high volume production make such devices ideal for point-of-care blood analysis and point-of-use chemical and fluid production, analysis and detection. Compared to conventional devices and techniques, these devices have a much smaller footprint and require minimum amount of resources to gather the same amount of information. Because of advances in plastic and silicon micromachining, such devices can take advantage of both the materials and the technologies to make microfluidic devices in large quantities and at lower cost. However, many macro-scale valve configurations are incompatible such small devices, and a need remains for micro-scale fluid control valves that can be opened and closed with precision.
Many typical microfluidic devices include a top cover in a parallel arrangement with plastic bottom having microchannels of sub-millimeter dimension. The top cover is commonly welded or joined to the bottom to make a sealed microchannel-based fluid handling system (see, U.S. Pat. Nos. 6,750,053 and 6,905,882). An essential aspect of control in microfluidic devices is the ability to stop and resume flow as desired. The devices often rely on capillary forces in the small microchannels to drive fluid flow in the microchannels. In some devices, surface properties, such as, e.g. hydrophobic and hydrophilic properties, have been used to influence flow rates. Because surface tension is often the most dominant of force acting on liquids in the microchannels, change in surface tension (or surface energy) of the liquid can be an effective way to control the flow. For example, U.S. Pat. No. 6,143,248 discloses a capillary stop valve, which uses a change of surface tension achieved by sudden expansion in capillary diameter to control a microfluidic flow
There are other methods to control flows, such as using chemical, thermal mechanical, optical, or electrostatic energy as disclosed by U.S. Pat. Nos. 6,561,224, 6,958,132, and 7,117,807. Out of these technologies, electrostatic energy has become a favored option because it can be more energy efficient than, e.g., the thermal technique. The principle of changing surface tension with electrical energy is called electro-capillarity or electrowetting (EW). Electrowetting by modulation of surface electrostatic charges can provide more precise control compared to techniques dependent on channel surface chemistry; and can be more reliable and easy to operate. Electro-capillarity, which is the basis of modern EW was demonstrated more than a century ago by Gabriel Lippmann when he showed that liquid mercury, in contact with an immiscible electrolyte solution, can be made to move inside a capillary by applying a voltage across the mercury-electrolyte interface. This idea was successfully applied to mercury-electrolyte systems, but a major drawback of this idea was electrolytic decomposition or Joule heating of aqueous electrolyte solutions, even when low voltages were applied. To avoid this situation, but still maintain the effect of an electric field, a dielectric layer can be introduced between the fluid and the electrolyte/electrode. This modification of the electrowetting technique is called electrowetting-on-dielectric (EWOD).
EW has been traditionally applied to systems where tiny droplets are manipulated in order to accomplish the pumping, mixing, valving, switching, and injecting actions in a precise manner. U.S. Pat. No. 6,911,132 described an apparatus for manipulating droplets. The apparatus is a single-sided electrode design in which all conductive elements are contained on one surface on which droplets are manipulated. An additional surface can be provided parallel with the first surface for the purpose of containing the droplets to be manipulated. Droplets are manipulated by performing electrowetting-based techniques in which electrodes contained on or embedded in the first surface are sequentially energized and de-energized in a controlled manner. The apparatus enables a number of droplet manipulation processes, including merging and mixing two droplets together, splitting a droplet into two or more droplets, sampling a continuous liquid flow by separating individually controllable droplets from the flow, and iterative binary or digital mixing of droplets to obtain a desired mixing ratio.
Similarly, U.S. Pat. No. 7,016,560 describes devices utilizing elements carried by a fluid in a microchannel to switch, attenuate, shutter, filter, or phase shift optical signals. In certain embodiments, a microchannel carries a gaseous or liquid slug that interacts with at least a portion of the optical power of an optical signal traveling through a waveguide. The microchannel may form part of the cladding of the waveguide, part of the core and the cladding, or part of the core only. The microchannel may also have ends or may be configured as a loop or continuous channel. The fluid devices may be self-latching or may be semi-latching. The fluid in the microchannel is moved using e.g., electrocapillarity, differential-pressure electrocapillarity, electrowetting, continuous electrowetting, electrophoresis, electroosmosis, dielectrophoresis, electro-hydrodynamic electrohydrodynamic pumping, magneto-hydrodynamic magnetohydrodynamic pumping, thermocapillarity, thermal expansion, dielectric pumping, and/or variable dielectric pumping.
In U.S. Pat. No. 6,130,098, the movement and mixing of microdroplets through microchannels is described employing microscale devices, comprising microdroplet transport channels, reaction regions, electrophoresis modules, and radiation detectors. The discrete droplets are differentially heated and propelled through etched channels. Electronic components are fabricated on the same substrate material, allowing sensors and controlling circuitry to be incorporated in the same device. The disclosed apparatus includes droplet transport channels having hydrophobic and hydrophilic regions selectively placed or patterned on the channel walls and surfaces, reaction chambers, gas inlet pathways and vents and detectors. An air chamber is included that is in connection with the transport channel to generate air bubbles inside liquid column to split and generate droplets. The transport microchannel is made from microfabricated silicon and glass substrates separated by a distance. One or more hydrophobic patches, regions or zones are provided in the droplet transport channel to separate a discrete amount of liquid from the sample so that it can be transported further for droplet ejection. This patent also discloses a method on creating and ejecting droplets from a liquid flow in microchannel by using a hydrophobic patch and bubble pressure in a side channel to generate droplets from liquid flow. A transport microchannel and side microchannels for generating droplets are made in a silicon substrate by bulk microfabrication to make the flow channels in silicon.
The advantages of EW (e.g., EWOD) are also extended to continuous flow systems wherein EW electrodes are set up along a microfluidic channel and are actuated as desired to control the fluid flow. Such EW-based systems can be made to incorporate valves and flow barriers in microchannels in order to stop and resume fluid flow as desired. A normally-closed valve can be in the form of a sudden expansion in the microchannel cross-section, or it can be made with a hydrophobic material that is selectively deposited in a narrow patch along the length of the microchannel. Such a hydrophobic patch can acts as a barrier to incoming fluid owing to large contact angle and surface tension energy on the patch.
In the above technologies, the fluids under control are typically kept separated by a slug of gas because the electrowetting forces are often inadequate to disrupt a continuous stream, e.g., without intervention of a mechanical valve. That is, once a flow is allowed at an electrowetting valve, the contact angle is zero and the electrowetting valve no longer has a fluid interface and contact angle to influence control of the flow. As a result of this deficiency, in many applications, a mechanical microvalve is needed to stop and start the flow of a continuous column of fluid in microfluidic channel.
Although electrowetting valve technologies offer some benefits in control of passive microfluidic flows, they typically suffer from an inability to reassert control over flow once they are traversed by a continuous fluid column. The optional incorporation of micromechanical valves can be prohibitively complex and expensive. In biochemistry or related applications, there is a need for a way to cyclically control flows, sample sizes and incubation times.
In view of the above, a need exists for an inexpensive and responsive valve for both starting and stopping microfluidic flows. It would be desirable to have a way to reestablish control of an electrowetting valve in the presence of a continuous fluid column across the valve. There is a need for a capillary to microscale valve that is volumetrically discrete and resettable. The present invention provides these and other features that will be apparent upon review of the following.